In medicine, the ability to obtain an image of a disease situs, especially one that is located depth-wise in a patient's tissue mass, is an important part of diagnosis and therapy. Cancer is an exemplary disease condition in which imaging is key. For example, with breast cancer, X-ray mammography is an important imaging modality used mainly for primary screening, while other imaging modalities such as ultrasonography and magnetic resonance offer second-stage detection that can provide useful information without having to perform an invasive procedure such as a biopsy. Unfortunately, X-ray mammography, in addition to using hazardous ionizing radiation and engendering patient discomfort, produces a high number of false-positives, has relatively low sensitivity, and sometimes produces false-negatives especially in radiographically dense breast tissue.
Another important imaging modality for various disease-related and other purposes is ultrasonic scanning, which has high sensitivity but low tissue specificity. Ultrasonic imaging is performed using an ultrasonic scanning machine to which a “probe” comprising one or more piezoelectric transducers is connected. Electrical pulses produced by the machine are converted by certain of the piezoelectric transducer(s) into corresponding ultrasound pulses of a desired frequency (usually between 2 and 18 MHz). The sound is focused either by the shape of the sending transducer(s), a “lens” in front of the transducer, or a complex set of control pulses from the ultrasonic scanning machine. Focusing produces a shaped acoustic wave propagating from the transducer. The sound wave enters the sample (e.g., a subject's body) and converges to focus at a desired depth in the sample. Most ultrasonic probes include a face member made of a material providing impedance matching for transmitting ultrasonic pulses efficiently into the subject's body. Also, a hydrogel is usually applied between the subject's skin and the face member of the probe for efficient propagation of sound waves to and from the probe. Portions of the sound wave are reflected from various tissue layers and structures in the sample, particularly from loci exhibiting density changes. Some of the reflected sound returns to the probe, in which certain transducer(s) convert the received sound into corresponding electrical pulses that are converted by the ultrasonic scanning machine into an image.
Photoacoustic imaging (PAI) is an emerging biomedical imaging modality based on the photoacoustic effect. In PAI, light pulses (often from a laser) are delivered to a target locus (“situs”) in or on a sample. Some of the pulse energy is absorbed at the situs and converted into heat. The transient heating causes a corresponding transient thermoelastic expansion of the situs, which produces a corresponding wideband ultrasonic emission from the situs. The generated ultrasonic waves are detected using one or more ultrasonic transducers that convert the detected waves into corresponding electrical pulses that are processed into corresponding images. The optical absorption of light by a biological sample is closely associated with certain physiological properties such as hemoglobin concentration and/or oxygen saturation. As a result, the magnitude of ultrasonic emission (the photoacoustic signal, which is proportional to the local energy deposition) from the situs reveals physiologically specific optical absorption contrast that facilitate formation of 2-D or 3-D images of the situs. Blood usually exhibits greater absorption than surrounding tissues, which provides sufficient endogenous contrast to allow PAI of blood vessels and tissues containing same. For example, PAI can produce high-contrast images of breast tumors in situ due to the greater optical absorption by the increased blood supply provided by the body to the tumor. Whereas conventional X-ray mammography and ultrasonography produce images of benign features as well as pathological features, PAI can produce information more specific to the malignant condition, such as enhanced angiogenesis at the tumor site.
Significant challenges currently limit PAI from widespread clinical use. For example, the geometrical constraints of the ultrasonic detector usually prevent direct illumination of the tissue, resulting in “dark” fields being present in locations where illumination is most needed. This situation is shown in FIG. 1, depicting a conventional arrangement of an ultrasonic detector array and two lasers. The respective beams produced by the lasers cross each other and thereby produce two dark fields, one being in the near field. Since the near field cannot be illuminated, a longer path length is required for ultrasonic waves from the illuminated region to the sensor array. FIG. 1 also shows that direct illumination of the situs becomes increasingly difficult as the physical dimensions of the detector increase, especially if the detector comprises an array of detector elements. Desirably, the detector should be acoustically coupled directly in front of the target situs tissue as the situs is being illuminated. But this is not possible in FIG. 1. In certain other conventional devices, illumination light is directed around a single-element detector. Unfortunately, these conventional devices require complicated optics and difficult setup procedures involving custom-made parts and sensitive alignments, and are too fragile to apply in a clinical setting. With these conventional devices it is also difficult to couple sufficient light to the small available illumination area, especially in view of the safety limits for exposure to laser light. In addition, most of these designs require application of complex deconvolution algorithms for making direct quantitative measurements.
Other limitations of conventional clinical PAI imaging include: (1) scan times are slow (>15 minutes) due to a lack of appropriate parallel receiving architecture; (2) conventional pulse echo (PE) images cannot be obtained simultaneously with the PAI images; and (3) the current PAI apparatus are bulky and expensive (most use a large laser that is difficult to transport).
Hence, it would be desirable to be able to obtain more informational images of a situs by both ultrasonography and PAI applied in a manner that produces real-time image information by these modalities that exploit different contrast mechanisms.